Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia
Open accessAbstract
Introduction: Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (LPL) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2′-O-methoxyethyl (2′-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with LPL mutation. Volanesorsen was well-tolerated and decreased patient’s TG levels (from >5000 mg/dL (56 mmol/L) to 350–500 mg/dL (4–5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice.
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Olezarsen has a more favorable side effect profile compared to Volanesorsen.
“Olezarsen also shows a more favorable side effect profile compared to its predecessor, Volanesorsen.”
From Efficacy and safety of Olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [9]
Section 2.2 (page not provided) reports injection-site reactions and thrombocytopenia among volanesorsen-treated patients, supporting the side-effect concern about that drug. The copy does not report olezarsen safety or compare the two drugs, so it does not establish that olezarsen has a more favorable side-effect profile. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOlezarsen appears to provide improved safety compared with volanesorsen while maintaining effective triglyceride reduction.
“Olezarsen appears to mitigate these risks while maintaining effective TG reduction [31][32][33]”
From Efficacy of Olezarsen in Severe Hypertriglyceridemia and Acute Pancreatitis Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [31]
Section 2.2 reports triglyceride reductions with volanesorsen and safety concerns, including platelet-count declines. The paper does not report olezarsen’s safety or triglyceride-lowering efficacy, so it cannot support the claimed improvement over volanesorsen while maintaining effective reduction (searched: olezarsen and comparative safety). (LLM, conf=0.78)
Experimental — accuracy not yet measuredVolanesorsen is effective in treating hypertriglyceridemia but is often associated with injection site reactions and a risk of thrombocytopenia, requiring regular platelet monitoring.
“While Volanesorsen is effective in treating hypertriglyceridemia, it is often associated with injection site reactions and a risk of thrombocytopenia, requiring regular platelet monitoring [9].”
From Efficacy and safety of Olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [9]
The targeted delivery of Olezarsen to hepatocytes reduces hypertriglyceridemia more effectively than current medications.
“The targeted delivery of the olezarsen to the hepatocyte reduces hypertriglyceridemia more effectively than current medications [8,9].”
From Efficacy and safety of Olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [9]
The Case Presentation and Expert Opinion discuss triglyceride reductions with volanesorsen, not olezarsen. Searches for olezarsen and hepatocyte-targeted delivery found no passage addressing olezarsen’s delivery or comparing its effectiveness with current medications. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Kolovou, G., Kolovou, V., & Katsiki, N.
- Affiliations
- Metropolitan Hospital (GR)
- AHEPA University Hospital (GR)
- Corresponding author
- Kolovou, Genovefa
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2022-02-13
- Volume
- 11
- Issue
- 4
- Pages
- 982
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC8880470
- OpenAlex
- W4212956691
- Cited by
- 33
- References
- 38
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 6
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Keywords
- volanesorsen, familial chylomicronemia syndrome, severe hypertriglyceridemia, antisense oligonucleotides, apolipoprotein C-III, triglyceride lowering, lipoprotein apheresis, thrombocytopenia, treatment efficacy and safety
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